Small-Cell Carcinoma With an Epidermal Growth Factor Receptor Mutation in a Never-Smoker With Gefitinib-Responsive Adenocarcinoma of the Lung
Small-Cell Carcinoma With an Epidermal Growth Factor Receptor Mutation in a Never-Smoker With Gefitinib-Responsive Adenocarcinoma of the Lung
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DOI：
10.3816/clc.2010.n.046
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发表时间：
2010-09-01
影响因子：
3.6
通讯作者：
Dudek, Arkadiusz Z.
中科院分区：
文献类型：
--
作者：
Alam, Naheed;Gustafson, Karen S.;Dudek, Arkadiusz Z.
表皮生长因子受体（EGFR）基因的激活突变在小细胞肺癌（SCLC）中极为罕见。在这里，我们报告了一例EGFR突变吉非替尼反应性非小细胞肺癌（NSCLC）的腺癌组织学，发生在从不吸烟的患者身上，随后被诊断为转移性SCLC，携带EGFR突变。尽管吉非替尼治疗原发性NSCLC使疾病控制超过3年，但患者随后发展为转移性SCLC至肝脏。表皮生长因子受体突变分析显示，在原发肺腺癌和转移性SCLC中均存在外显子21 L858R激活突变。我们假设SCLC要么是从先前诊断的NSCLC进化而来，要么两者都来自一个共同的前体。进一步对这些组织学上不同的肿瘤进行比较分子分析，将有助于更好地了解EGFR在不吸烟者SCLC发病机制中的潜在作用，以及EGFR突变SCLC亚克隆的选择作为非小细胞肺癌中EGFR抑制剂获得性耐药的不寻常机制的作用。
Activating mutations in the epidermal growth factor receptor (EGFR) gene are extremely rare in small-cell lung cancer (SCLC). Here, we present a case of an EGFR-mutant gefitinib-responsive non-small-cell lung cancer (NSCLC) of adenocarcinoma histology occurring in a never-smoker followed by subsequent diagnosis of metastatic SCLC carrying an EGFR mutation. Although gefitinib therapy of the primary NSCLC resulted in disease control for over 3 years, the patient subsequently developed metastatic SCLC to the liver. Epidermal growth factor receptor mutation analysis revealed that the exon 21 L858R activating mutation was present in both the original lung adenocarcinoma and the metastatic SCLC. We hypothesize that SCLC either evolved from the previously diagnosed NSCLC or that both arose from a common precursor. Further comparative molecular analysis of these histologically distinct tumors would be of value to better understand the potential role of EGFR in the pathogenesis of SCLC in never-smokers, and the role of selection for an EGFR-mutant SCLC subclone as an unusual mechanism of acquired resistance to EGFR inhibitors in NSCLC.